title: Hydrogen-bonded complexes and blends of poly(acrylic acid) and methylcellulose: nanoparticles and mucoadhesive films for ocular delivery of riboflavin.
abstract: Poly(acrylic acid) (PAA) and methylcellulose (MC) are able to form hydrogen-bonded interpolymer complexes (IPCs) in aqueous solutions. In this study, the complexation between PAA and MC is explored in dilute aqueous solutions under acidic conditions. The formation of stable nanoparticles is established, whose size and colloidal stability are greatly dependent on solution pH and polymers ratio in the mixture. Poly(acrylic acid) and methylcellulose are also used to prepare polymeric films by casting from aqueous solutions. It is established that uniform films can be prepared by casting from polymer mixture solutions at pH 3.4-4.5. At lower pHs (pH < 3.0) the films have inhomogeneous morphology resulting from strong interpolymer complexation and precipitation of polycomplexes, whereas at higher pHs (pH 8.3) the polymers form fully immiscible blends because of the lack of interpolymer hydrogen-bonding. The PAA/MC films cast at pH 4 are shown to be non-irritant to mucosal surfaces. These films provide a platform for ocular formulation of riboflavin, a drug used for corneal cross-linking in the treatment of keratoconus. An in vitro release of riboflavin as well as an in vivo retention of the films on corneal surfaces can be controlled by adjusting PAA/MC ratio in the formulations.
authors.affiliation: School of Pharmacy, University of Reading, Whiteknights, PO Box 224, Reading RG6 6AD, Berkshire, UK.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Khutoryanskaya
authors.forename: Peter W J
authors.initials: PW
authors.lastname: Morrison
authors.forename: Serzhan K
authors.initials: SK
authors.lastname: Seilkhanov
authors.forename: Marat N
authors.initials: MN
authors.lastname: Mussin
authors.forename: Elvira K
authors.initials: EK
authors.lastname: Ozhmukhametova
authors.forename: Tolebai K
authors.initials: TK
authors.lastname: Rakhypbekov
authors.forename: Vitaliy V
authors.initials: VV
authors.lastname: Khutoryanskiy
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D060433:Administration, Ophthalmic; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D049851:Gastropoda / Q000187:drug effects; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008747:Methylcellulose / Q000737:chemistry*; D009092:Mucous Membrane / Q000187:drug effects; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D011817:Rabbits; D012256:Riboflavin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012996:Solutions
chemical_list: D000180:Acrylic Resins; D012996:Solutions; C006903:carbopol 940; D008747:Methylcellulose; D012256:Riboflavin
keywords: hydrogen bonding; interpolymer complexes; mucoadhesive films; ocular drug delivery; riboflavin